Integration of Longitudinal Clinical, Immunologic, and Environmental Data for Enhanced Disease Monitoring and Management in Pemphigus Vulgaris: A Case Study

Abstract

We present a case study of a patient with pemphigus vulgaris using an integrative, longitudinal approach to resolve the identities and potential contributions of a network of environmental exposures of possible clinical relevance in a genetically predisposed individual. Our comprehensive methodology tracked exposomal factors, disease evolution, and biological variables across the patient's lifespan. Our patient reported multiple predisease onset exposures historically associated with pemphigus vulgaris, including multiple psychosocial and physical/chemical stressors. After disease onset, despite standard pharmacologic treatment, disease activity fluctuated widely. Notably, within 14 months after substantial dietary changes and body mass index reduction, the patient achieved long-lasting complete clinical remission off therapy. Our results reinforce the significance of the gene-environment interplay in pemphigus vulgaris, emphasizing the role of diet in autoimmune regulation. This study serves as proof of concept regarding the power of detailed longitudinal mapping of disease expression and contemporaneous monitoring of the "exposome" and "behaviorome" to reveal previously unrecognized disease-modifying elements and suggest targeted and personalized lifestyle modifications to augment established treatments. Our study design and strategy offer a template for a hyperpersonalized approach to medicine through comprehensive lifespan data collection and integrative analyses to yield enhanced insights into disease development, with the goal of uncovering actionable interventions in future clinical care settings in the management of autoimmune disorders.

Keywords: Autoimmunity; Exposome; Patient empowerment; Pemphigus; Personalized medicine.

Graphical abstract

Figure 1

The patient’s exposures to environmental factors previously associated with triggering PV in the literature summarized chronologically according to the stage(s) of life where the exposure occurred. Pink backgrounds denote environmental factors thought to contribute to/exacerbate disease (light pink = before disease onset, dark pink = after disease onset), whereas green backgrounds denote those suspected to improve disease status. MVA, motor vehicle accident; NSAID, nonsteroidal anti-inflammatory drug; PV, pemphigus vulgaris.

Figure 2

Aggregate illustration of changes in the patient’s clinical (BMI, PDAI, treatment[s], therapy status, disease activity/status) and immunologic/biologic (anti- DSG1, anti-DSG3, and anti-TPO autoantibody levels) parameters over time in juxtaposition with significant, potentially disease-altering events such as the initiation of pharmacologic treatment, initially with glucocorticoids and later with rituximab, or the patient’s self-directed dietary and lifestyle modifications. The left vertical axis reflects autoantibody levels in IU/ml and illustrates the levels of anti-DSG1, anti-DSG3, and anti-TPO antibodies at various points in time. The right vertical axis reflects the patient’s BMI in kg/m², taken directly from copies of the patient’s medical records. “Active” disease was defined as the presence of 3 or more nontransient lesions (lasting >1 week) and/or the extension of existing lesions. PR = partial remission defined as patients with transient lesions only (lasting less than 1 week). LTR = long-term remission defined as the absence of new or established lesions for greater than 6 months (Sielski et al, 2022). MM = more than minimal therapy, defined as patients receiving >10 mg/day of prednisone, IVIg, cyclosporin, dapsone, rituximab, or other biologic agents. M = minimal therapy defined as prednisone doses ≤10 mg/day and/or minimal adjuvant therapy for at least 2 months (Murrell et al, 2008). O = off therapy, reserved for patients not receiving any systemic therapy. BMI, body mass index; Dex, dexamethasone; DSG, desmoglein; IVIg, intravenous Ig; MMF, mycophenolate mofetil; PDAI, Pemphigus Disease Area Index; TPO, thyroid peroxidase.

Figure 3

Longitudinal inflammatory profiling of patient before and after dietary and lifestyle modifications. Left vertical axis reflects values for both ESR in mm/h and CRP in mg/l. Right vertical axis reflects values for serum hemoglobin A1C levels (in %). PR = partial remission defined as patients with transient lesions only (lasting less than 1 week). LTR = long-term remission defined as the absence of new or established lesions for greater than 6 months (Sielski et al, 2022). CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.